ReviewHormones (Athens, Greece)2026
Lipodystrophies and female reproduction: pathophysiology, clinical spectrum, and management across the reproductive lifespan.
Review in Hormones (Athens, Greece), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundLipodystrophies represent a heterogeneous group of rare disorders characterized by partial or generalized loss of adipose tissue, leading to severe metabolic derangements and endocrine dysfunction. In women, these disorders are frequently accompanied by reproductive abnormalities ranging from hypogonadotropic amenorrhea to hyperandrogenism and polycystic ovary syndrome-like phenotypes.
objectiveTo summarize current knowledge linking adipose-tissue dysfunction and female reproductive health, focusing on mechanistic pathways, clinical manifestations, fertility outcomes, contraception, pregnancy complications, and therapeutic perspectives including leptin replacement.
methodsA comprehensive review of PubMed and guideline literature (1996-2025) was performed, prioritizing official recommendations, registry data, and recent mechanistic and clinical studies.
resultsProfound leptin deficiency in generalized lipodystrophy leads to hypothalamic suppression of gonadotropin-releasing hormone (GnRH) and amenorrhea, whereas hyperinsulinemia and androgen excess dominate partial forms, producing anovulation and infertility. Metreleptin therapy restores ovulatory cycles in leptin-deficient women and improves metabolic control, while pregnancy carries heightened risks of gestational diabetes, pre-eclampsia, and pancreatitis. Oral estrogens exacerbate hypertriglyceridemia; thus, progestin-only or non-hormonal contraception is preferred, and transdermal estrogen may be considered for hormone replacement.
conclusionsFemale reproductive dysfunction in lipodystrophy results from complex interactions between leptin, insulin, and gonadal steroid pathways. A multidisciplinary approach is required to optimize metabolic and reproductive outcomes, while prospective data on fertility and pregnancy under metreleptin remain crucial for future practice.
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